Project Summary/Abstract Aging is a risk factor for cardiovascular disease (CVD), and women who experience premature or early menopause have a 50% greater risk for CVD-related death compared with women who experience menopause at the typical age. Indeed, CVD increases aggressively after menopause and is the leading cause of mortality in women in the US. Autonomic and blood pressure (BP) dysregulation, often demonstrated in postmenopausal women, is associated with CVD. Although literature suggests that estrogen is cardioprotective for premenopausal women, little is known regarding how the early loss of sex hormones in premature and early menopause effect BP regulation. This application for a Mentored Research Scientist Development Award (K01) is designed to advance knowledge important for understanding mechanisms contributing to increased CVD in aging women and support the career of Dr. Manda L Keller-Ross, DPT, PhD, an Assistant Professor in the Department of Rehabilitation Medicine, in the Medical School at the University of Minnesota. Dr. Keller- Ross is the PI of the Cardiovascular Research and Rehabilitation Laboratory, where the proposed research will take place. The long-term objectives of this proposal are to determine mechanisms that contribute to greater risk of CVD in premature and early menopausal women. Specifically, Dr. Keller-Ross aims to determine mechanisms driving autonomic BP regulation in premature and early menopausal women near the age of menopausal onset (Aim 1). She will then determine mechanisms driving autonomic BP regulation in women who have lived ?10 years without functioning ovaries to determine the long-term effects (Aim 2). This proposal is in line with the mission of the NIA, to understand the nature of the aging process in women and how the loss of sex hormones contributes to the number one killer in women, CVD. Dr. Keller-Ross has a clinical research background and seeks mentored training and skill development to enhance her knowledge on biology of aging, women?s health specific to the cardiovascular system and menopause and advanced techniques to measure autonomic function. She will accomplish her career development goals through a combination of formal coursework, mentored skill and technique development for microneurography to measure muscle sympathetic nerve activity and noninvasive measures of baroreflex function and the empirical research described above. Dr. Keller-Ross has established an interdisciplinary mentorship team to guide her in these research and training activities. This committee has senior-level expertise in aging research in females, autonomic regulation of BP research and biostatistical analysis. They are eminently qualified and fully committed to assisting Dr. Keller-Ross to further her training, research and career path and achieve her career objectives. With this training, Dr. Keller-Ross is poised to become a leading scientist in cardiovascular health in aging women, producing research that is directly translatable to clinical practice devising strategic preventative and rehabilitative therapies to improve cardiovascular health, specific to aging women.